Epigenetic Mechanisms Driving Tumor Supportive Microenvironment Differentiation and Function: A Role in Cancer Therapy?

Abstract

The tumor microenvironment (TME) plays a central role in tumor development and drug resistance. Within TME, the stromal cell subset, called cancer-associated fibroblasts, is a heterogeneous population originating from poorly characterized precursors. Since cancer-associated fibroblasts do not acquire somatic mutations, other mechanisms like epigenetic regulation, could be involved in the development of these cells and in the acquisition of tumor supportive phenotypes. Moreover, such epigenetic modulations have been correlated to the emergence of an immunosuppressive microenvironment facilitating tumor evasion. These findings underline the need to deepen our knowledge on epigenetic mechanisms driving TME development and function, and to understand the impact of epigenetic drugs that could be used in future to target both tumor cells and their TME.

Keywords::

• cancer
• cancer-associated fibroblasts
• epigenetic
• microenvironment

Financial & competing interests disclosure

M Sylvestre is a recipient of a fellowship from the Ligue contre le Cancer and the Région Bretagne. K Tarte and D Roulois are supported by the Fondation ARC pour la Recherche sur le Cancer and the INCA PLBIO 17-219, CALYS. D Roulois is supported by La Ligue contre le Cancer and by the Université de Rennes 1 (AAP défis scientifiques). D Roulois is a member of the Réseau Niches et Epigénétiques des Tumeurs from the Cancéropole Grand Ouest. We thank Cancéropôle Grand Ouest to support the Niches and Epigenetics of Tumors network, http://www.canceropole-grandouest.com. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors would like to thank A Martin for her comments and proofreading.

Additional information

Funding

M Sylvestre is a recipient of a fellowship from the Ligue contre le Cancer and the Région Bretagne. K Tarte and D Roulois are supported by the Fondation ARC pour la Recherche sur le Cancer and the INCA PLBIO 17-219, CALYS. D Roulois is supported by La Ligue contre le Cancer and by the Université de Rennes 1 (AAP défis scientifiques). D Roulois is a member of the Réseau Niches et Epigénétiques des Tumeurs from the Cancéropole Grand Ouest. We thank Cancéropôle Grand Ouest to support the Niches and Epigenetics of Tumors network, http://www.canceropole-grandouest.com. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors would like to thank A Martin for her comments and proofreading.